Impact of MYD88<sup>L265P</sup> mutation status on histological transformation of Waldenström Macroglobulinemia

Zanwar, Saurabh; Abeykoon, Jithma P.; Durot, Éric; King, Rebecca; Burbano, Gabriela E. Perez; Kumar, Santosh; Gertz, Morie A.; Quinquenel, Anne; Delmer, Alain; Gonsalves, Wilson I.; Cornillet‐Lefèbvre, Pascale; He, Rong; Warsame, Rahma; Buadi, Francis K.; Novak, Anne J.; Greipp, Patricia T.; Inwards, David J.; Habermann, Thomas M.; Micallef, Ivana N.; Go, Ronald S.; Muchtar, Eli; Kourelis, Taxiarchis; Dispenzieri, Angela; Lacy, Martha Q.; Dingli, David; Nowakowski, Grzegorz S.; Thompson, Carrie A.; Johnston, Patrick B.; Thanarajasingam, Gita; Bennani, N. Nora; Witzig, Thomas E.; Villasboas, José C.; Leung, Nelson; Lin, Yi; Kyle, Robert A.; Rajkumar, S. Vincent; Ansell, Stephen M.; Le‐Rademacher, Jennifer; Kapoor, Prashant

doi:10.1002/ajh.25697

Cited by 37 publications

(37 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, the IPI and the R-IPI were assessed. 5,6 The presence of MYD88 L265P mutation was tested by allele-specific polymerase chain reaction on bone marrow samples at diagnosis of WM 9 .…”

Section: Patients and Data Collection For Development Of The Prognostmentioning

confidence: 99%

“…3,4 Patients who experience HT have an inferior survival compared to patients who do not transform during their disease course. 3,5 Patients with transformed WM are mainly treated with strategies used in de novo DLBCL but exhibit low cure rates, with a median survival from the time of HT ranging from 16 to 32 months. [3][4][5] However, as some patients experience prolonged survival, identifying those with high-risk features in order to select them for therapeutic intensification and/or novel agents is important.…”

Section: Introductionmentioning

confidence: 99%

“…3,5 Patients with transformed WM are mainly treated with strategies used in de novo DLBCL but exhibit low cure rates, with a median survival from the time of HT ranging from 16 to 32 months. [3][4][5] However, as some patients experience prolonged survival, identifying those with high-risk features in order to select them for therapeutic intensification and/or novel agents is important. In a previous study of 77 patients, we identified elevated LDH and time to HT above 5 years as possible predictors of shorter survival 4 but there is a need to develop an accurate predictive model for overall survival in a larger cohort of transformed WM patients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A prognostic index predicting survival in transformed Waldenström macroglobulinemia

et al. 2020

Self Cite

View full text Add to dashboard Cite

Histological transformation into diffuse large B-cell lymphoma is a rare complication in patients with Waldenström macroglobulinemia (WM) usually associated with a poor prognosis. The objective of this study was to develop and validate a prognostic index for survival in transformed WM patients. Through this multicenter, international collaborative effort, we developed a scoring system based on data from 133 patients with transformed WM who were evaluated between 1995 and 2016 (training cohort). Univariate and multivariate analyses were used to propose a prognostic index with 2-year survival after transformation as an end-point. For external validation, a data set of 67 patients was used to evaluate the performance of the model (validation cohort). By multivariate analysis, three adverse covariates were identified as independent predictors of 2-year survival after transformation: elevated serum LDH (2 points), platelet count < 100 x 109/L (1 point) and any previous treatment for WM (1 point). Three risk groups were defined: low-risk (0-1 point, 24% of patients), intermediate-risk (2-3 points, 59%, hazard ratio (HR) = 3.4) and high-risk (4 points, 17%, HR = 7.5). Two-year survival rates were 81%, 47%, and 21%, respectively (P < 0.0001). This model appeared to be a better discriminant than the International Prognostic Index (IPI) and the revised IPI (R-IPI). We validated this model in an independent cohort. This easy-to-compute scoring index is a robust tool that may allow identification of groups of transformed WM patients with different outcomes and could be used for improving the development of risk-adapted treatment strategies.

show abstract

Section: Patients and Data Collection For Development Of The Prognostmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A prognostic index predicting survival in transformed Waldenström macroglobulinemia

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Classically, it is believed that LPL without MYD88 mutation progresses to DLBCL with a higher probability than LPL cases with MYD88 mutation [36,37]. Nevertheless, in our hands wild type MYD88 LPL cases are exceptional (only two documented cases in our archive) and none of them progressed into a more aggressive lymphoma.…”

Section: Plos Onementioning

confidence: 43%

Lymphoplasmacytic lymphoma associated with diffuse large B-cell lymphoma: Progression or divergent evolution?

et al. 2020

View full text Add to dashboard Cite

Aim Lymphoplasmacytic lymphoma (LPL) is an indolent mature B-cell-neoplasm with involvement of the bone marrow. At least 90% of LPLs carry MYD88-L265P mutation and some of them (~10%) transform into diffuse large B-cell-lymphoma (DLBCL). Material and methods Over the past 15 years we have collected 7 cases where the both LPL and DLBCL were diagnosed in the same patient. Clinical records, analytical data and histopathological specimens were reviewed. FISH studies on paraffin-embedded tissue for MYC, BCL2 and BCL6 genes were performed, as well as MYD88-L265P mutation and IGH rearrangement analysis by PCR. A mutational study was done by massive next generation sequencing (NGS). Results There were 4 women and 3 men between 36–91 years of age. Diagnoses were made simultaneously in 4 patients. In two cases the LPL appeared before the DLBCL and in the remaining case the high-grade component was discovered 5 years before the LPL. In 6 cases both samples shared the MYD88-L265P mutation. IGH rearrangement analysis showed overlapping features in two of 6 cases tested. Mutational study was evaluable in three cases for both samples showing shared and divergent mutations. Conclusions These data suggest different mechanisms of DLBCL development in LPL patients.

show abstract

“…Interestingly, the “double WT” group had lower levels of BM involvement and lower IgM levels compared to the others [ 107 ]. MYD88 WT status has also been reported as an independent risk factor for large cell transformation of WM [ 108 ]. However, a large retrospective study of WM patients treated mainly with rituximab-alkylator based regimens showed that MYD88 mutational status had no significant impact on long term survival [ 109 ].…”

Section: Future Directionsmentioning

confidence: 99%

Immunoglobulin M Paraproteinaemias

Girard

Soekojo

Ooi

et al. 2020

Cancers

View full text Add to dashboard Cite

Monoclonal paraproteinaemia is an increasingly common reason for referral to haematology services. Paraproteinaemias may be associated with life-threatening haematologic malignancies but can also be an incidental finding requiring only observation. Immunoglobulin M (IgM) paraproteinaemias comprise 15–20% of monoclonal proteins but pose unique clinical challenges. IgM paraproteins are more commonly associated with lymphoplasmacytic lymphoma than multiple myeloma and can occur in a variety of other mature B-cell neoplasms. The large molecular weight of the IgM multimer leads to a spectrum of clinical manifestations more commonly seen with IgM paraproteins than others. The differential diagnosis of B-cell and plasma cell dyscrasias associated with IgM gammopathies can be challenging. Although the discovery of MYD88 L265P and other mutations has shed light on the molecular biology of IgM paraproteinaemias, clinical and histopathologic findings still play a vital role in the diagnostic process. IgM secreting clones are also associated with a number of “monoclonal gammopathy of clinical significance” entities. These disorders pose a novel challenge from both a diagnostic and therapeutic perspective. In this review we provide a clinical overview of IgM paraproteinaemias while discussing the key advances which may affect how we manage these patients in the future.

show abstract

Impact of MYD88^L265P mutation status on histological transformation of Waldenström Macroglobulinemia

Cited by 37 publications

References 31 publications

A prognostic index predicting survival in transformed Waldenström macroglobulinemia

A prognostic index predicting survival in transformed Waldenström macroglobulinemia

Lymphoplasmacytic lymphoma associated with diffuse large B-cell lymphoma: Progression or divergent evolution?

Immunoglobulin M Paraproteinaemias

Contact Info

Product

Resources

About

Impact of MYD88L265P mutation status on histological transformation of Waldenström Macroglobulinemia

Cited by 37 publications

References 31 publications

A prognostic index predicting survival in transformed Waldenström macroglobulinemia

A prognostic index predicting survival in transformed Waldenström macroglobulinemia

Lymphoplasmacytic lymphoma associated with diffuse large B-cell lymphoma: Progression or divergent evolution?

Immunoglobulin M Paraproteinaemias

Contact Info

Product

Resources

About

Impact of MYD88^L265P mutation status on histological transformation of Waldenström Macroglobulinemia